Structural biology has played a key role in revealing the molecular basis of life in the past 50 years. Thanks to several landmark technical advances, the field has made significant strides from determining static macromolecular structures at atomic resolution to observing functional dynamics of protein structures spanning a vast conformational space and beyond the crystal lattice. As innovations in structural biology continue to transform modern biology and medicine, this chapter presents a perspective on past triumphs, current challenges, and future directions with a focus on how to capture protein structure dynamics using experimental and analytical methods.